Neuromuscular manifestations of pediatric endocrine disorders: A 25-Year Narrative Review of Muscular and Neurological Involvement, Clinical Reversibility, and Age-Specific Differences

Background: Endocrine disorders in childhood profoundly affect skeletal muscle and the nervous system through hormonal, metabolic, and inflammatory pathways. Although numerous studies have explored these associations, the cumulative evidence on clinical presentation, pathophysiology, and reversibility across endocrine axes remains fragmented.

Methods: This narrative review synthesized findings from 88 studies published between 2000 and 2025—comprising randomized trials, cohorts, and cross-sectional analyses—retrieved from PubMed, Scopus, and Google Scholar. Studies focusing on children and adolescents with endocrine disorders exhibiting muscular or neurological manifestations were included. Data were organized into tables describing (1) acute and chronic muscular features, (2) neurological involvement, and (3) reversibility following hormonal therapy. Study quality was graded using Cochrane and GRADE criteria.

Results: Analysis of 63 core studies within the introduction and results revealed a wide range of neuromuscular outcomes. Hypothyroidism emerged as the leading cause of pediatric myopathy and developmental delay, with early levothyroxine replacement resulting in complete reversal of muscle weakness and near-normal cognitive function. Hyperthyroidism presented mainly with proximal myopathy and thyrotoxic periodic paralysis, both rapidly reversible after achieving euthyroidism. Cushing’s syndrome and critical illness–related corticosteroid insufficiency (CIRCI) were strongly associated with catabolic myopathy, showing partial recovery due to persistent mitochondrial and proteasomal injury.

Vitamin D deficiency and hypoparathyroidism accounted for most acute, reversible neuromuscular crises characterized by tetany, hypocalcemic seizures, and hypotonia. Growth hormone deficiency (GHD) produced sustained reductions in lean mass and muscle endurance, while GH replacement led to significant structural and metabolic recovery. Diabetes mellitus demonstrated early neuropathic and myopathic changes driven by oxidative stress and glucose fluctuation, reversible with tight glycemic control. Neurologically, congenital hypothyroidism, adrenal crises, and prolonged hypercortisolism remained major causes of developmental and cognitive impairment, whereas GH and vitamin D deficiency produced milder, reversible neurocognitive deficits.  Overall, 75% of disorders exhibited at least partial neuromuscular reversibility, with the best outcomes observed in hormone-deficient states corrected within early childhood.

Conclusion: Pediatric endocrine disorders exhibit diverse but interconnected neuromuscular and neurological manifestations. Early hormonal replacement and metabolic correction substantially enhance reversibility and long-term neuro-muscular outcomes, while catabolic and inflammatory disorders such as Cushing’s and CIRCI lead to incomplete recovery. Routine neuromuscular monitoring should be incorporated into endocrine management to optimize recovery and preserve function.